Multiple myeloma (MM) is a malignancy characterized by an accumulation of clonal plasma cells (see, e.g., Palumbo et al., New England J Med., 364(11): 1046-1060 (2011), and Lonial et al., Clinical Cancer Res., 17(6): 1264-1277 (2011)). Current therapies for MM often cause remissions, but nearly all patients eventually relapse and die (see, e.g., Lonial et al., supra, and Rajkumar, Nature Rev. Clinical Oncol., 8(8): 479-491 (2011)). Allogeneic hematopoietic stem cell transplantation has been shown to induce immune-mediated elimination of myeloma cells; however, the toxicity of this approach is high, and few patients are cured (see, e.g., Lonial et al., supra, and Salit et al., Clin. Lymphoma, Myeloma, and Leukemia, 11(3): 247-252 (2011)). Currently, there are no clinically effective, FDA-approved monoclonal antibody or autologous T-cell therapies for MM (see, e.g., Richardson et al., British J. Haematology, 154(6): 745-754 (2011), and Yi, Cancer Journal, 15(6): 502-510 (2009)).
Adoptive transfer of T-cells genetically modified to recognize malignancy-associated antigens is showing promise as a new approach to treating cancer (see, e.g., Morgan et al., Science, 314(5796): 126-129 (2006); Brenner et al., Current Opinion in Immunology, 22(2): 251-257 (2010); Rosenberg et al., Nature Reviews Cancer, 8(4): 299-308 (2008), Kershaw et al., Nature Reviews Immunology, 5(12): 928-940 (2005); and Pule et al., Nature Medicine, 14(11): 1264-1270 (2008)). T-cells can be genetically modified to express chimeric antigen receptors (CARs), which are fusion proteins comprised of an antigen recognition moiety and T-cell activation domains (see, e.g., Kershaw et al., supra, Eshhar et al., Proc. Natl. Acad. Sci. USA, 90(2): 720-724 (1993), and Sadelain et al., Curr. Opin. Immunol., 21(2): 215-223 (2009)).
For B-cell lineage malignancies, extensive progress has been made in developing adoptive T-cell approaches that utilize anti-CD19 CARs (see, e.g., Jensen et al., Biology of Blood and Marrow Transplantation, 16: 1245-1256 (2010); Kochenderfer et al., Blood, 116(20): 4099-4102 (2010); Porter et al., The New England Journal of Medicine, 365(8): 725-733 (2011); Savoldo et al., Journal of Clinical Investigation, 121(5): 1822-1826 (2011), Cooper et al., Blood, 101(4): 1637-1644 (2003); Brentjens et al., Nature Medicine, 9(3): 279-286 (2003); and Kalos et al., Science Translational Medicine, 3(95): 95ra73 (2011)). Adoptively transferred anti-CD19-CAR-transduced T-cells have cured leukemia and lymphoma in mice (see, e.g., Cheadle et al., Journal of Immunology, 184(4): 1885-1896 (2010); Brentjens et al., Clinical Cancer Research, 13(18 Pt 1): 5426-5435 (2007); and Kochenderfer et al., Blood, 116(19): 3875-3886 (2010)). In early clinical trials, adoptively transferred T-cells transduced with anti-CD19 CARs eradicated normal and malignant B-cells in patients with leukemia and lymphoma (see, e.g., Kochenderfer et al., Blood, 116(20): 4099-4102 (2010); Porter et al., supra, Brentjens et al., Blood, 118(18): 4817-4828 (2011); and Kochenderfer et al., Blood, Dec. 8, 2011 (epublication ahead of print (2012)). CD19, however, is only rarely expressed on the malignant plasma cells of multiple myeloma (see, e.g., Gupta et al., Amer. J. Clin. Pathology, 132(5): 728-732 (2009); and Lin et al., Amer. J. Clin. Pathology, 121(4): 482-488 (2004)).
Thus, there remains a need for compositions that can be used in methods to treat multiple myeloma. This invention provides such compositions and methods.